Sustained and repeated mouth opening leads to development of painful temporomandibular disorders involving macrophage/microglia activation in mice

摘要: Temporomandibular disorder (TMD) is a set of heterogeneous musculoskeletal conditions involving the temporomandibular joint (TMJ) and/or masticatory muscles. Up to 33% population has had at least 1 symptom TMD with 5% 10% them requiring treatment. Common symptoms include limited jaw movement, sound, and pain in orofacial area. Once becomes chronic, it can be debilitating comorbidities that greatly reduce one's overall quality life. However, underlying mechanism unclear because multicausative nature disease. Here, we report novel mouse model where bite block was placed between upper lower incisors such mouth kept maximally open for 1.5 hours per day 5 days. After sustained opening, mice developed persistent mechanical allodynia TMJ dysfunction. At cellular level, found masseter muscle dystrophy, increased proteoglycan deposition hypertrophic chondrocytes mandibular condyle. Increased F4/80 macrophages were also observed muscles posterior synovium. We ATF3 neuronal injury trigeminal ganglia. Microglia activation subnucleus caudalis. Inhibiting macrophage microglia colony stimulating factor-1 receptor inhibitor prevented development allodynia, but not This study suggests opening an extended period during dental treatments or oral intubations may risk chronic inflammation associated tissue system contributes pain.